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Frontiers in Cardiovascular Medicine 2022Several 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are...
BACKGROUND
Several 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are reported to be associated with coronary artery disease (CAD) susceptibility but independent of dyslipidemia. This study investigated whether these 9p21.3 variants influenced lipid profiles.
METHODS AND RESULTS
By searching the PubMed and Cochrane databases, 101,099 individuals were included in the analysis. The consistent finding for the rs1333049 C allele on lipid profiles increased the triglyceride (TG) levels. Moreover, the rs4977574 G allele and the rs10757274 G allele, respectively, increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. However, the rs10811661 C allele largely reduced LDL-C levels. Subgroup analyses indicated that the effects of the rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele on lipid profiles were stronger in Whites compared with Asians. In contrast, the effect of the rs10811661 C allele on lipid profiles was stronger in Asians compared with Whites.
CONCLUSION
The rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele of lncRNA, and the rs10811661 G allele of CDKN2A/2B had a significant influence on lipid levels, which may help the understanding of the underlying mechanisms between 9p21.3 variants and CAD.
PubMed: 36158791
DOI: 10.3389/fcvm.2022.946289 -
Scars, Burns & Healing 2017Keloid disease (KD) is common and often refractory to treatment. Definition of the genetic mechanisms of KD can lead to a better understanding of the disease and suggest... (Review)
Review
BACKGROUND
Keloid disease (KD) is common and often refractory to treatment. Definition of the genetic mechanisms of KD can lead to a better understanding of the disease and suggest more effective treatment strategies.
OBJECTIVES
To quantitatively estimate the association between KD susceptibility and the -509C/T polymorphism in the TGF-β1 gene.
METHODS
PubMed, Embase and CNKI databases were searched using a combination of the Medical Subject Headings (MeSH) and relevant words in titles. Analyses were performed with STATA 12.0.
RESULTS
Five case-control studies encompassing a total of 564 keloid cases and 620 healthy controls were pooled in the final meta-analysis. Among the five studies, no significant association was detected between the TGF-β1 -509C/T polymorphism and KD under all of the five genetic models (allele comparison, heterozygote comparison, homozygote comparison, dominant model and recessive model) for the overall analyses and for the subgroup analyses based on DNA extraction method, participant ethnicity and group size. When stratified by study quality, three high-quality studies showed significant association under allele comparison and homozygote model (C versus T: OR = 0.80, 95% confidence interval [CI] = 0.65-0.98, = 0.03; I = 0%, = 0.64; CC versus TT: OR = 0.62, 95% CI = 0.41-0.94, = 0.02; I = 0%, = 0.79); while two moderate-quality studies showed significant association under allele comparison, homozygote model and recessive model (C versus T: OR = 1.52, 95% CI = 1.15-2.01, = 0.004; I = 39%, = 0.20; CC versus TT: OR = 2.14, 95% CI = 1.24-3.70, = 0.02; I = 19%, = 0.27; CC versus CT+TT: OR = 2.04, 95% CI = 1.29-3.24, = 0.002; I = 0%, = 0.35).
CONCLUSIONS
The current meta-analysis suggests that the TGF-β1 -509C/T polymorphism is not associated with KD susceptibility. High-quality and large-scale studies are needed to validate our findings.
PubMed: 29799568
DOI: 10.1177/2059513117709943 -
Medicine Aug 2018Published studies have reported conflicting and heterogeneous results regarding the association between human leukocyte antigen (HLA)-DRB1 polymorphisms and alopecia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Published studies have reported conflicting and heterogeneous results regarding the association between human leukocyte antigen (HLA)-DRB1 polymorphisms and alopecia areata (AA). This study aimed to review and quantitatively analyze the association between HLA-DRB1 polymorphisms and AA.
METHODS
In this study, all relevant publications were searched through December 2016. Odds ratios (ORs) and confidence intervals (CIs) for comparisons between case and control groups were calculated. Stata 14.0 software was used to perform statistical analysis. This research does not require formal ethical approval because the data used in this analysis do not involve personal information and thus do not affect privacy.
RESULTS
Twelve articles were identified. For HLA-DRB1*04 and HLA-DRB1*16 polymorphisms, the OR (95% CIs) was 1.49 (1.24-1.78) and 1.61 (1.08-2.41), and P was <.01 and <.01, respectively. For HLA-DRB1*0301, HLA-DRB1*09, and HLA-DRB1*13 polymorphisms, the OR (95% CIs) was 0.42 (0.28-0.63), 0.74 (0.55-0.99), and 0.62 (0.40-0.98), and P was <.01, <.01, and <.01, respectively. Statistical evidence revealed no publication bias (P > .05).
CONCLUSION
The present meta-analysis suggested that HLA-DRB1*04 and HLA-DRB1*16 polymorphisms might be associated with increased AA risk, while HLA-DRB1*0301, HLA-DRB1*09, and HLA-DRB1*13 polymorphisms might decrease the AA risk. Studies with adequate methodological quality on gene-gene and gene-environment interactions are needed to validate the results in the future.
Topics: Alleles; Alopecia Areata; Case-Control Studies; Genetic Predisposition to Disease; HLA-DRB1 Chains; Humans; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 30095639
DOI: 10.1097/MD.0000000000011790 -
Oncotarget Aug 2016mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to... (Meta-Analysis)
Meta-Analysis Review
mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed a systematic review and updated meta-analysis of the available evidence regarding the relationship between mTOR single nucleotide polymorphisms (SNPs) and cancer risk. Up to November 2015, 23 original publications were identified covering 20 mTOR SNPs, of which seven SNPs (rs2536, rs2295080, rs1883965, rs1034528, rs17036508, rs3806317 and rs1064261) were included in the final meta-analysis. We estimated the summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for mTOR polymorphisms and cancer risk, and used the model-free approach to investigate the biological effect of each polymorphism. Our meta-analysis found that rs1883965, rs1034528, and rs17036508 were correlated with increased cancer risk in the complete over-dominant model (rs1883965 GA versus GG/AA: fixed-effects OR=1.15, 95% CI 1.02-1.29; rs1034528 GC versus GG/CC: fixed-effects OR=1.30, 95% CI 1.13-1.48; rs17036508 TC versus CC/TT: fixed-effects OR=1.23, 95% CI 1.06-1.43). Stratifying analyses by cancer type, we found that the rs2295080 G allele was associated with a significantly higher risk of acute leukemia in the recessive model (GG versus GT/TT: fixed-effects OR=2.08, 95% CI 1.34-3.22) and a lower risk of genitourinary cancers in the dominant model (TG/GG versus TT: fixed-effects OR=0.77, 95% CI 0.68-0.86). Interestingly, further expression analysis showed that homozygous variant genotype carriers of rs1883965, rs1034528 and rs17036508 had lower mTOR transcript levels, based on HapMap data.
Topics: Alleles; Computational Biology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genotype; Humans; Neoplasms; Odds Ratio; Polymorphism, Single Nucleotide; TOR Serine-Threonine Kinases
PubMed: 27462867
DOI: 10.18632/oncotarget.10805 -
BMJ (Clinical Research Ed.) Sep 2016To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.
DESIGN
Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.
DATA SOURCES
Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.
RESULTS
We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.
CONCLUSIONS
We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015015969.
Topics: Adiposity; Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Genetic Predisposition to Disease; Genotype; Humans; Obesity; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 27650503
DOI: 10.1136/bmj.i4707 -
Reumatologia Clinica 2023To describe the demographic and clinical features, as well as the frequency of the HLA-B*51 allele in Behçet disease (BD) patients in Latin American countries. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To describe the demographic and clinical features, as well as the frequency of the HLA-B*51 allele in Behçet disease (BD) patients in Latin American countries.
METHODS
A systematic literature review of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines was conducted without performing a meta-analysis. We included observational studies (cross-sectional or cohort) of BD patients fulfilling the International Study Group for BD classification criteria and reported the demographic, clinical, and laboratory features of the disease in adult patients.
RESULTS
Twelve studies were included in the SLR. Information from 532 patients across 5 Latin American countries was included for the analysis. Mean age at disease diagnosis was 33 years, 58.3% were female and 41.7% male; most patients were non-Caucasian. The most common clinical manifestations were recurrent oral ulcers and genital ulcers, followed by skin, eye, joint, neurological, gastrointestinal, vascular, and cardiac involvement. The prevalence of BD was described in 2 studies, 1 conducted in Brazil that reported a prevalence of .3/100,000 inhabitants, and another in Colombia with a prevalence of 1.1/100,000 inhabitants. The frequency of HLA-B*51 allele in BD patients was 38%, 30.1%, and 9% in Argentina, Brazil, and Mexico, respectively.
CONCLUSIONS
The prevalence of BD in the Latin American countries seems to be low, as well as the frequency of HLA-B*51 allele. However, the strength of association between HLA-B*51 and BD remains high in our population. The key clinical features of BD are like those reported in countries/regions where BD is endemic.
Topics: Adult; Humans; Male; Female; Behcet Syndrome; Cross-Sectional Studies; Latin America; HLA-B Antigens; Prevalence
PubMed: 37661116
DOI: 10.1016/j.reumae.2022.12.005 -
PloS One 2013To evaluate evidence on the association between CYP2D6 genotype and tamoxifen response through. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate evidence on the association between CYP2D6 genotype and tamoxifen response through.
DESIGN
Systematic review and meta-analysis of prospective, cross-sectional and case-control studies published to 2012. For each study, relative risks and 95% confidence intervals were extracted and pooled with a fixed and random effects model. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed.
DATA SOURCES
PubMed (inception-2012) and EMBASE (inception-2012).
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Criteria for inclusion were studies reporting breast cancer outcomes in patients treated with tamoxifen and genotyped for polymorphisms in the CYP2D6 gene.
RESULTS
Twenty-five studies of 13,629 individuals were identified, of which 22 investigated the association of CYP2D6 genotype with outcomes in breast cancer women all receiving tamoxifen treatment ("treatment-only" design). Three randomized trials evaluated the effect of CYP2D6 genotype on tamoxifen response ("effect modification" design). In analysis of treatment-only studies, the relative risk (RR) of all-cause mortality (>307 events in 4,936 patients) for carriers of a CYP2D6 reduced function allele was 1.11 (95% confidence interval (CI): 0.94 to 1.31) compared to individuals with normal/increased function CYP2D6 alleles. When we investigated a composite outcome including all-cause mortality and surrogate endpoints for overall survival (>307 events in 6,721 patients), carriers of a CYP2D6 reduced function allele had a RR of 1.27 (95% CI: 1.11 to 1.45). From two randomized trials that permitted effect-modification analysis, one had only 154 patients and showed evidence of effect modification of tamoxifen by CYP2D6 genotype for distant recurrence but was directionally opposite to that predicted, whereas a larger trial of 2,537 patients failed to show evidence of effect modification for breast cancer-free interval (P values for interaction 0.02 and 0.44, respectively).
CONCLUSIONS
Based on these findings, there is insufficient evidence to recommend CYP2D6 genotyping to guide tamoxifen treatment.
Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Breast Neoplasms; Cross-Sectional Studies; Cytochrome P-450 CYP2D6; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Polymorphism, Genetic; Prospective Studies; Survival Analysis; Tamoxifen; Treatment Outcome
PubMed: 24098545
DOI: 10.1371/journal.pone.0076648 -
Association of maternal AGTR1 polymorphisms and preeclampsia: a systematic review and meta-analysis.The Journal of Maternal-fetal &... Dec 2012Systematic review and meta-analysis to investigate the association between maternal AGTR1 gene single nucleotide polymorphisms (SNPs) and preeclampsia (PE). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Systematic review and meta-analysis to investigate the association between maternal AGTR1 gene single nucleotide polymorphisms (SNPs) and preeclampsia (PE).
METHODS
A systematic literature search was performed using PubMed, EMBASE, Scopus, and HuGE Literature Finder databases. The review was conducted according to PRISMA guidelines. Summary odds ratios (ORs) for the allelic and genotypic contrasts were calculated and compared to indicate the most appropriate genetic model for the polymorphism of interest. Among-study heterogeneity was assessed using the I(2) statistic and publication bias was evaluated visually using funnel plots.
RESULTS
Seven maternal SNPs investigated with PE were found, but only AGTR1 +1166A>C accumulated sufficient evidence for meta-analysis. Summary ORs calculated from eight studies (10 populations involving 845 PE cases and 1150 controls) did not reveal an association between the +1166A>C polymorphism and PE (allelic OR = 1.19, 95% CI: 0.96-1.47). No evidence of publication bias and among-study heterogeneity was detected.
CONCLUSIONS
meta-analysis findings did not support AGTR1 +1166A>C as a susceptibility locus for PE. Other AGTR1 SNPs require more study.
Topics: Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Mothers; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Receptor, Angiotensin, Type 1
PubMed: 22758920
DOI: 10.3109/14767058.2012.708370 -
Frontiers in Genetics 2023Chronic obstructive pulmonary disease (COPD) affects approximately 400 million people worldwide and is associated with high mortality and morbidity. The effect of and...
Chronic obstructive pulmonary disease (COPD) affects approximately 400 million people worldwide and is associated with high mortality and morbidity. The effect of and gene polymorphisms on COPD risk has not been fully characterized. To investigate the association of and polymorphisms with COPD risk. A systematic search was conducted on 9 databases to identify studies published in English and Chinese. The analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines (PRISMA). The pooled OR and 95% CI were calculated to evaluate the association of and polymorphisms with COPD risk. The I test, Q test, Egger's test, and Begg's test were conducted to determine the level of heterogeneity and publication bias of the included studies. In total, 857 articles were retrieved, among which 59 met the inclusion criteria. The rs1051740 polymorphism (homozygote, heterozygote, dominant, recessives, and allele model) was significantly associated with high risk of COPD risk. Subgroup analysis revealed that the rs1051740 polymorphism was significantly associated with COPD risk among Asians (homozygote, heterozygote, dominant, and allele model) and Caucasians (homozygote, dominant, recessives, and allele model). The rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with a low risk of COPD. Subgroup analysis showed that the rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Asians. The rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk. Subgroup analysis showed that the rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk among Caucasians. The rs1138272 polymorphism (heterozygote and dominant model) was significantly associated with COPD risk. Subgroup analysis suggested that the rs1138272 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Caucasians. The C allele in rs1051740 among Asians and the CC genotype among Caucasians may be risk factors for COPD. However, the GA genotype in rs2234922 may be a protective factor against COPD in Asians. The GG genotype in rs1695 and the TC genotype in rs1138272 may be risk factors for COPD, especially among Caucasians.
PubMed: 37284064
DOI: 10.3389/fgene.2023.1128985 -
Pain Physician Sep 2023Responsiveness to opioid analgesics differs among patients with acute postoperative pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Responsiveness to opioid analgesics differs among patients with acute postoperative pain.
OBJECTIVE
Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids.
STUDY DESIGN
An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain.
METHODS
PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021.
RESULTS
Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human μ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms.
LIMITATIONS
Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis.
CONCLUSIONS
In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia.
KEY WORDS
Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
Topics: Humans; Analgesics, Opioid; Catechol O-Methyltransferase; Cytochrome P-450 CYP3A; Pain, Postoperative; Polymorphism, Single Nucleotide
PubMed: 37774182
DOI: No ID Found